Clinical Memory Research Unit, Department of Clinical Sciences, Skånes universitetssjukhus, VE Minnessjukdomar, Lund University, 205 02, Malmö, Sweden.
Neuroscience Biomarkers, Janssen Research & Development, La Jolla, CA, USA.
Alzheimers Res Ther. 2022 May 14;14(1):67. doi: 10.1186/s13195-022-01005-8.
Recent advances in disease-modifying treatments highlight the need for accurately identifying individuals in early Alzheimer's disease (AD) stages and for monitoring of treatment effects. Plasma measurements of phosphorylated tau (p-tau) are a promising biomarker for AD, but different assays show varying diagnostic and prognostic accuracies. The objective of this study was to determine the clinical performance of a novel plasma p-tau217 (p-tau217) assay, p-tau217+, and perform a head-to-head comparison to an established assay, plasma p-tau217, within two independent cohorts METHODS: The study consisted of two cohorts, cohort 1 (27 controls and 25 individuals with mild-cognitive impairment [MCI]) and cohort 2 including 147 individuals with MCI at baseline who were followed for an average of 4.92 (SD 2.09) years. Receiver operating characteristic analyses were used to assess the performance of both assays to detect amyloid-β status (+/-) in CSF, distinguish MCI from controls, and identify subjects who will convert from MCI to AD dementia. General linear and linear mixed-effects analyses were used to assess the associations between p-tau and baseline, and annual change in Mini-Mental State Examination (MMSE) scores. Spearman correlations were used to assess the associations between the two plasma measures, and Bland-Altmann plots were examined to assess the agreement between the assays.
Both assays showed similar performance in detecting amyloid-β status in CSF (plasma p-tau217+ AUC = 0.91 vs plasma p-tau217 AUC = 0.89), distinguishing MCI from controls (plasma p-tau217+ AUC = 0.91 vs plasma p-tau217 AUC = 0.91), and predicting future conversion from MCI to AD dementia (plasma p-tau217+ AUC = 0.88 vs p-tau217 AUC = 0.89). Both assays were similarly related to baseline (plasma p-tau217+ rho = -0.39 vs p-tau217 rho = -0.35), and annual change in MMSE scores (plasma p-tau217+r = -0.45 vs p-tau217r = -0.41). Correlations between the two plasma measures were rho = 0.69, p < 0.001 in cohort 1 and rho = 0.70, p < 0.001 in cohort 2. Bland-Altmann plots revealed good agreement between plasma p-tau217+ and plasma p-tau217 in both cohorts (cohort 1, 51/52 [98%] within 95%CI; cohort 2, 139/147 [95%] within 95%CI).
Taken together, our results indicate good diagnostic and prognostic performance of the plasma p-tau217+ assay, similar to the p-tau217 assay.
疾病修饰治疗的最新进展突出表明需要准确识别早期阿尔茨海默病（AD）阶段的个体，并监测治疗效果。磷酸化 tau（p-tau）的血浆测量是 AD 的有前途的生物标志物，但不同的检测方法显示出不同的诊断和预后准确性。本研究的目的是确定新型血浆 p-tau217（p-tau217）检测（p-tau217+）的临床性能，并在两个独立队列中与已建立的检测（血浆 p-tau217）进行头对头比较。
该研究由两个队列组成，队列 1（27 名对照和 25 名轻度认知障碍 [MCI] 个体）和队列 2，队列 2 包括基线时有 147 名 MCI 个体，平均随访 4.92（SD 2.09）年。使用受试者工作特征分析来评估两种检测方法在检测脑脊液中淀粉样β状态（+/-）、区分 MCI 与对照以及识别将从 MCI 转化为 AD 痴呆的患者方面的性能。使用一般线性和线性混合效应分析来评估 p-tau 与基线和每年 MMSE 评分变化之间的关联。使用 Spearman 相关系数评估两种血浆测量之间的关联，并使用 Bland-Altmann 图评估检测之间的一致性。
两种检测方法在检测脑脊液中的淀粉样β状态方面表现相似（血浆 p-tau217+ AUC = 0.91 与血浆 p-tau217 AUC = 0.89），区分 MCI 与对照（血浆 p-tau217+ AUC = 0.91 与血浆 p-tau217 AUC = 0.91），并预测从 MCI 向 AD 痴呆的未来转化（血浆 p-tau217+ AUC = 0.88 与 p-tau217 AUC = 0.89）。两种检测方法均与基线相似（血浆 p-tau217+ rho = -0.39 与 p-tau217 rho = -0.35），以及每年 MMSE 评分的变化（血浆 p-tau217+r = -0.45 与 p-tau217r = -0.41）。两种血浆测量之间的相关性在队列 1 中为 rho = 0.69，p < 0.001，在队列 2 中为 rho = 0.70，p < 0.001。Bland-Altmann 图显示，在两个队列中，血浆 p-tau217+ 和血浆 p-tau217 之间具有良好的一致性（队列 1，51/52 [98%]在 95%CI 内；队列 2，139/147 [95%]在 95%CI 内）。
综上所述，我们的结果表明，血浆 p-tau217+ 检测具有良好的诊断和预后性能，与 p-tau217 检测相似。
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